Search

Background. The contribution of human rhinovirus (HRV) to severe acute respiratory illness (ARI) is unclear. Objective. To assess the association between HRV species detection and ARI hospitalizations. Methods. Children <5 years old hospitalized for ARI were prospectively enrolled between December 2003 and April 2005 in 3 US counties. Asymptomatic controls were enrolled between December 2003 and March 2004 and between October 2004 and April 2005 in clinics. Nasal and throat swab samples were tested for HRV and other viruses (ie, respiratory syncytial virus, human metapneumovirus, parainfluenza virus, and influenza virus) by reverse-transcription-polymerase chain reaction, and genetic sequencing identified HRV species and types. HRV species detection was compared between controls and patients hospitalized during months in which controls were enrolled. Results. A total of 1867 children with 1947 ARI hospitalizations and 784 controls with 790 clinic visits were enrolled and tested for HRV. The HRV-A detection rate among participants ≤24 months old was 8.1% in the hospitalized group and 2.2% in the control group (P = .009), and the HRV-C detection rates among those ≤6 months old were 8.2% and 3.9%, respectively (P = .002); among younger children, the detection rates for both species were similar between groups. The HRV-B detection rate was ≥1%. A broad diversity of HRV types was observed in both groups. Clinical presentations were similar among HRV species. Compared with children infected with other viruses, children with HRV detected were similar for severe hospital outcomes and more commonly had histories or diagnoses of asthma or wheezing. Conclusions. HRV-A and HRV-C were associated with ARI hospitalization and serious illness outcomes. [ABSTRACT FROM AUTHOR]

Background. Routine rotavirus vaccination of US infants began in 2006. We conducted active, populationbased surveillance for rotavirus gastroenteritis hospitalizations in 3 US counties to assess vaccine impact. Methods. Children <36 months old hospitalized with diarrhea and/or vomiting were enrolled from January through June each year during the period 2006-2009 and tested for rotavirus. Age-stratified rates of hospitalization for rotavirus infection were compared with corresponding vaccination coverage among a control group of children with acute respiratory illness. To assess direct and indirect benefits, vaccination coverage rates in the control group were multiplied by vaccine effectiveness estimates to calculate expected reductions in the rate of hospitalization for rotavirus infection. Rotavirus serotypes were compared across years. Results. Compared with 2006, a significant reduction in rates of hospitalization for rotavirus infection (P < .001) was observed in 2008 among all age groups. There was an 87% reduction in the 6-11-month-old age group (coverage, 77%), a 96% reduction in the 12-23-months-old age group (coverage, 46%), and a 92% reduction in the 24-35-month-old age group (coverage, 1%), which exceeded reductions expected on the basis of coverage and vaccine effectiveness estimates. Age-specific rate reductions were nearly equivalent to those expected on the basis of age-specific vaccine coverage in 2009. Predominant strains varied annually: G1P[8] (91%) in 2006; G1P[8] (45%) and G12P[8] (36%) in 2007; G1P[8] (89%) in 2008; and G3P[8] (43%), G2P[4] (34%), and G9P[8] (27%) in 2009. Conclusions. Rotavirus vaccination has dramatically decreased rates of hospitalization for rotavirus infection among children in these US counties. In 2008, reductions were prominent among both vaccine-eligible age groups and older, largely unvaccinated children; the latter likely resulted from indirect protection. Although rates among age groups eligible for vaccination remained low in 2009, indirect benefits disappeared. [ABSTRACT FROM AUTHOR]

Background. Human metapneumovirus (HMPV) is a leading cause of acute respiratory illness (ARI) in children. Population-based incidence rates and comprehensive clinical characterizations of disease have not been established. Methods. We conducted population-based prospective surveillance for 2 years in 2 US counties of HMPV infection among children !5 years old who were hospitalized with ARI or fever. Nasal and throat specimens obtained with swabs were tested for HMPV by real-time reverse-transcription polymerase chain reaction and genotyped. Results. Forty-two (3.8%) of 1104 children tested positive for HMPV. The overall annual rate of HMPVassociated hospitalizations per 1000 children !5 years old was 1.2 (95% confidence interval [CI], 0.9-1.6). This rate was highest among infants 0-5 months old (4.9 per 1000 [95% CI, 2.9-7.2]), followed by children 6-11 months old (2.9 per 1000 [95% CI, 1.4-4.7]). The annual rate of hospitalization for HMPV infection was less than that for respiratory syncytial virus infection but similar to that for influenza and parainfluenza virus 3 infection in all age groups. The mean age of children hospitalized with HMPV infection was 6 months. Bronchiolitis, pneumonia, and asthma were the most common diagnoses among children with HMPV infection. All 4 HMPV subgroups were detected during both years at both sites. HPMV infection was most prominent from March through May. Conclusion. HMPV was detected in 3.8% of children hospitalized with ARI or fever, with a population incidence similar to that of influenza virus and parainfluenza virus 3. [ABSTRACT FROM AUTHOR]

Background. Because a previous rotavirus vaccine was associated with intussusception, new rotavirus vaccines are monitored postlicensure for any such association. Accurate background intussusception rates are needed to determine whether the number of cases observed after vaccination exceeds that expected by chance. Previously, intussusception rates were obtained from inpatient discharge databases. We sought to determine the rate of intussusception among infants managed only with short-stay or emergency department care. Methods. Intussusception cases occurring in infants were identified retrospectively at 3 children's hospitals from January 2001 through March 2006, a period without rotavirus vaccine use, by a search of discharge, billing, and radiology databases for International Classification of Diseases, Ninth Revision, Clinical Modification code 560.0 (intussusception) and procedure codes and by review of medical records. Results. Of 156 infants with intussusception fulfilling Brighton level 1 criteria, 81 (52%) were billed as inpatients, 68 (44%) as short-stay patients, and 7 (4%) as emergency department patients only. The use of only inpatients assigned code 560.0 underestimated the total number of level 1 cases at the hospitals by 44%. The mean annual intussusception rate for the hospitals' catchment counties was 49.3 cases per 100,000 live births (inpatient cases: 27.1 cases per 100,000 live births; short-stay or emergency department cases: 22.3 cases per 100,000 live births). Conclusions. Intussusception rates based solely on inpatient discharge databases could underestimate the true incidence of level 1 intussusception by >40%. Background rates used for assessment of risk after vaccination should account for cases managed only with short-stay or emergency department care. [ABSTRACT FROM AUTHOR]

Background: Respiratory syncytial virus (RSV) infection is the most common respiratory viral infection resulting in hospitalizations in infants worldwide. Illness severity is likely multifactorial; however, unlike other viral infections, both type 1 and type 2 cytokine responses have been implicated in severe disease.Methods: We measured RSV-specific cytokine responses ex vivo during primary RSV infection in the blood of 18 infants with polymerase chain reaction-confirmed RSV infection. To focus on primary RSV infection, subjects were all<9 months old. RSV-specific cytokine responses were measured at 3 time points during acute primary RSV infection and at 1 memory time point 3-6 months later.Results: RSV-specific interferon (IFN)- gamma responses were detected in 10 of 18 of infants. Infants with mild disease had higher RSV-specific IFN- gamma memory responses than did those with moderate or severe disease. No consistent correlations between RSV-specific IFN- gamma responses and corticosteroid administration were observed. RSV-specific interleukin (IL)-4 or IL-5 responses to primary RSV infection were detectable in 5 of 18 and 8 of 15 infants, respectively.Conclusions: During primary RSV infection, many infants demonstrated RSV-specific IFN- gamma responses. The strongest IL-4 and IL-5 responses were detected in 3 infants with severe disease, suggesting that type 2 responses may contribute to the pathogenesis of severe disease. [ABSTRACT FROM AUTHOR]

Background. Rhinoviruses frequently cause the common cold but have not been considered important causes of acute respiratory hospitalizations in children. Methods. A population-based surveillance study was performed among children <5 years of age who were hospitalized with respiratory symptoms or fever and who resided within counties encompassing Nashville, Tennessee, or Rochester, New York, from October 2000 through September 2001. Data collected included questionnaires, nasal and throat swabs for viral culture and polymerase chain reaction testing, and chart review. Rates of rhinovirus-associated hospitalizations were calculated. Results. Of 592 children enrolled, 156 (26%) were rhinovirus positive, representing 4.8 (95% confidence interval [CI], 4.3-5.2) rhinovirus-associated hospitalizations/1000 children. Age- specific rates per 1000 children were 17.6 (95% CI, 14.9-20.6) for 0-5-month olds, 6.0 (95% CI, 5.0-7.0) for 6-23-month-olds, and 2.0 (95% CI, 1.6, 2.4) for 24-59-month-olds (P<0.1). Children with a history of wheezing/asthma had significantly more rhinovirus- P<.01 associated hospitalizations than those without a history (25.3/1000 children [95% CI, 21.6-29.5/1000 children] vs. 3.1/1000 children [95% CI, 2.7-3.5/1000 children]). Conclusions. Rhinoviruses were associated with nearly 5 hospitalizations/1000 children <5 years of age and were highest in children with a history of wheezing/asthma. [ABSTRACT FROM AUTHOR]

Premature infants and those with chronic lung disease or congenital heart disease are at high risk of severe respiratory syncytial virus (RSV) disease. Palivizumab (Synagis), a humanized anti-RSV monoclonal antibody, has been used extensively since 1998 to prevent severe RSV disease in high-risk infants. To monitor for possible palivizumab-resistant mutants, an immunofluorescence binding assay that predicts palivizumab neutralization of RSV was developed. RSV isolates were collected at 8 US sites from 458 infants hospitalized for RSV disease (1998-2002). Palivizumab bound to all 371 RSV isolates able to be evaluated, including 25 from active-palivizumab recipients. The palivizumab epitope appears to be highly conserved, even in infants receiving prophylaxis with palivizumab. [ABSTRACT FROM AUTHOR]

We compared the rates of detection of respiratory viruses by reverse-transcription polymerase chain reaction (RT-PCR) and by conventional viral culture in 668 combined nasal and throat samples from a prospective, multicenter, population-based study of acute respiratory tract infections among hospitalized children aged <5 years. RT-PCR increased the yield of viral identification by 2-fold, compared with that of culture alone. The increased sensitivity of viral detection by RT-PCR will yield better estimates of the population burden of viral respiratory infections. [ABSTRACT FROM AUTHOR]

Reports that the influenza outbreaks in health care facilities can have a potentially devastating consequences for immunocompromised persons in the U.S. Evidence of the mechanisms of influenza transmission; Sources of health-care facility-acquired influenza; Vaccination of hospitalized patients at risk for influenza-related complications.

Looks at the circulation patterns of human respiratory syncytial virus (HRSV) strains in five distinct communities during an epidemic season in North America by analysis of the G protein gene of group A and B HRSV strains. Phylogenetic analysis of HRSV group A and B strains; Distribution patterns of HRSV genotypes within and between communities; Indication that virus strains can be transmitted over broad geographic regions during a single epidemic season.

The cotton rat model of respiratory syncytial virus infection was used to study immunization with viral glycoproteins. Animals immunized with the purified attachment protein (G) or the fusion protein (F) developed complete pulmonary resistance, but only partial nasal resistance, to challenge with respiratory syncytial virus. Antibody produced to the G protein neutralized virus, whereas antibody to the F protein neutralized virus and also inhibited fusion of infected cells. There was no evidence of enhanced pulmonary pathology in any immunized group. [ABSTRACT FROM PUBLISHER]

Quantitative shedding patterns of respiratory syncytial virus in 40 infants hospitalized with acute disease of the lower respiratory tract were determined for elucidation of the pathophysiology of infection with the virus. Nasal wash specimens were collected on admission and daily thereafter and were tested for the presence and quantities of respiratory syncytial virus. The following pattern of shedding was observed. (1) The virus was shed for prolonged periods. For the first seven days of hospitalization, 92%–100% of the infants tested continued to shed virus. At discharge 87% were still shedding the virus. (2) Respiratory syncytial virus was present in high titer in the nasal secretions obtained at the time of admission. The mean titer in these samples was 5.0 log10 tcid50. (3) The titer of respiratory syncytial virus did not fall during the first few days of hospitalization, despite clinical improvement of the infants. Neither peak nor admission titers of virus could be correlated with age or with the severity of disease. However, the mean admission titer in patients with bronchiolitis appeared to be significantly higher than that in those with pneumonia. [ABSTRACT FROM PUBLISHER]

A simple method for the isolation of respiratory syncytial virus (RSV) is reported; it is relatively rapid and results in a high frequency of recovery of virus. A nasal secretion specimen with high titers of virus is inoculated at the bedside onto susceptible cell lines to avoid loss of viral infectivity due to liability of the virus. During an outbreak of RSV, viral specimens were obtained by this method from all young children admitted to the hospital with lower respiratory tract disease. RSV or influenza A virus was recovered from 89% of these 45 children. RSV was isolated from 87% of those with pneumonia. RSV was recovered 60% less often from specimens obtained simultaneously by conventional nasopharyngeal swabs. Identification of RSV cytopathic effect was more rapid with use of the bedside nasal wash method and was accomplished in an average of four days. Hence, this information was available to the clinicician when it was still useful in the management of the patient's illness. [ABSTRACT FROM AUTHOR]

The relationship between respiratory syncytial virus (RSV) strain and disease severity was assessed in 265 hospitalized infants over a 3-year period (1988–1991). A severity index of clinical and physiologic parameters was used to grade illness severity. Multivariate analysis of 134 infants infected with group A RSV strains and 131 infants infected with group B strains indicated that prematurity, underlying medical conditions, group A RSV infection, and age ⩽3 months were independently associated with severe disease. Odds ratios for severe disease for these risk factors were 1.83, 2.84, 3.26, and 4.39, respectively. Among infants without underlying medical conditions, group B RSV infection rarely required ventilatory support, in contrast to group A infections (1/90 vs. 13/107; P < .006), and had significantly lower severity indices (mean ± SD, 0.6 ± 9 vs. 1.3 ± 1.9; P = .05). Results confirm earlier findings that group A RSV infection results in greater disease severity than group B infection among hospitalized infants. [ABSTRACT FROM PUBLISHER]

Monoclonal antibodies and ribonuclease protection were used to analyze antigenic and genomic diversity among 42 isolates of group A respiratory syncytial virus (RSV) from studies of nosocomial RSV carried out at the University of Rochester during the 1974–1975 and 1975–1976 RSV seasons. Three distinct subgroups or lineages and a total of 12 viral variants were present. Against this background of diversity, an outbreak was recognized that included 13 indistinguishable isolates occurring during a 2-week period. This outbreak accounted for 6 of the 8 infants with nosocomial infection. In contrast to the limited diversity of the nosocomial isolates, isolates from the 10 infants with community-acquired infection included 8 variants. Like those from community outbreaks of RSV, isolates ofRSV from hospitalized patients are virologically heterogeneous. However, discrete outbreaks associated with transmission of a single strain can occur. [ABSTRACT FROM PUBLISHER]

Direct sequence analysis of polymerase chain reaction-amplified DNA fragments from the large tegument protein (LTP) gene of human herpesvirus 6 (HHV-6) was performed with use of uncultured peripheral blood mononuclear cells (PBMCs) from four mother/infant pairs. In two cases, LTP gene sequences were identical in paired mother/infant specimens, thus suggesting that mother-to-infant transmission of HHV-6 may have occurred. The genetic stability of HHV-6 strains was confirmed by the fact that there was no difference between amplified DNA fragments from sequential PBMC samples from two of two infants analyzed. In contrast, a change in the amplified viral strain was detected in an infant who had reinfection with HHV-6 variant B (HHV-6B). Furthermore, HHV-6B strains concurrently amplified from saliva and PBMCs from an adult were found to be different. The data suggest that HHV-6 may be frequently transmitted from mother-to-infant and that reinfection with HHV-6B may occur. [ABSTRACT FROM PUBLISHER]

These guidelines deal with the evaluation of anti-infective drugs for the treatment of respiratory tract infections. Five clinical entities are described: streptococcal pharyngitis and tonsillitis, otitis media, sinusitis, bronchitis, and pneumonia. A wide variety of microorganisms are potentially pathogenetic in these diseases; these guidelines focus on the bacterial infections. Inclusion of a patient in a trial of a new drug is based on the clinical entity, with the requirement that a reasonable attempt will be made to establish a specific microbial etiology. Microbiologic evaluation of efficacy requires isolation of the pathogen and testing for in vitro susceptibility. Alternatively, surrogate markers may be used to identify the etiologic agent. The efficacy of new drugs is evaluated with reference to anticipated response rates. Establishment of the microbial etiology of respiratory tract infections is hampered by the presence of “normal flora” of the nose, mouth, and pharynx, which may include asymptomatic carriage of potential pathogens. This issue is addressed for each category of infection described. For example, it is suggested that for initial phase 2 trials of acute otitis media and acute sinusitis tympanocentesis or direct sinus puncture be used to collect exudate for culture. Acute exacerbations of chronic bronchitis also present difficulties in the establishment of microbial etiology. These guidelines suggest that clinical trials employ an active control drug but leave open the possibility of a placebo-controlled trial. For pneumonia, the guidelines suggest the identification and enrollment of patients by the clinical type of pneumonia, e.g., atypical pneumonia or acute bacterial pneumonia, rather than by etiologic organism or according to whether it was community or hospital acquired. For each respiratory infection, the clinical response is judged as cure, failure, or indeterminate. Clinical improvement is not acceptable unless quantitative response measures can be applied. [ABSTRACT FROM PUBLISHER]